| 1. |
|
|
| 2. |
|
|
| 3. |
- Hjorth-Hansen, A. K., et al.
(författare)
-
Real-time automatic quantification of left ventricular function by hand-held ultrasound devices in patients with suspected heart failure : a feasibility study of a diagnostic test with data from general practitioners, nurses and cardiologists
- 2022
-
Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 12:10
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To evaluate the feasibility and reliability of hand-held ultrasound (HUD) examinations with real-time automatic decision-making software for ejection fraction (autoEF) and mitral annular plane systolic excursion (autoMAPSE) by novices (general practitioners), intermediate users (registered cardiac nurses) and expert users (cardiologists), respectively, compared to reference echocardiography by cardiologists in an outpatient cohort with suspected heart failure (HF). DESIGN: Feasibility study of a diagnostic test. SETTING AND PARTICIPANTS: 166 patients with suspected HF underwent HUD examinations with autoEF and autoMAPSE measurements by five novices, three intermediate-skilled users and five experts. HUD results were compared with a reference echocardiography by experts. A blinded cardiologist scored all HUD recordings with automatic measurements as (1) discard, (2) accept, but adjust the measurement or (3) accept the measurement as it is. PRIMARY OUTCOME MEASURE: The feasibility of automatic decision-making software for quantification of left ventricular function. RESULTS: The users were able to run autoEF and autoMAPSE in most patients. The feasibility for obtaining accepted images (score of ≥2) with automatic measurements ranged from 50% to 91%. The feasibility was lowest for novices and highest for experts for both autoEF and autoMAPSE (p≤0.001). Large coefficients of variation and wide coefficients of repeatability indicate moderate agreement. The corresponding intraclass correlations (ICC) were moderate to good (ICC 0.51-0.85) for intra-rater and poor (ICC 0.35-0.51) for inter-rater analyses. The findings of modest to poor agreement and reliability were not explained by the experience of the users alone. CONCLUSION: Novices, intermediate and expert users were able to record four-chamber views for automatic assessment of autoEF and autoMAPSE using HUD devices. The modest feasibility, agreement and reliability suggest this should not be implemented into clinical practice without further refinement and clinical evaluation. TRIAL REGISTRATION NUMBER: NCT03547076.
|
|
| 4. |
- Nemec, K, et al.
(författare)
-
Functional modulation of PTH1R activation and signaling by RAMP2
- 2022
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 119:32, s. e2122037119-
-
Tidskriftsartikel (refereegranskat)abstract
- Receptor-activity-modifying proteins (RAMPs) are ubiquitously expressed membrane proteins that associate with different G protein–coupled receptors (GPCRs), including the parathyroid hormone 1 receptor (PTH1R), a class B GPCR and an important modulator of mineral ion homeostasis and bone metabolism. However, it is unknown whether and how RAMP proteins may affect PTH1R function. Using different optical biosensors to measure the activation of PTH1R and its downstream signaling, we describe here that RAMP2 acts as a specific allosteric modulator of PTH1R, shifting PTH1R to a unique preactivated state that permits faster activation in a ligand-specific manner. Moreover, RAMP2 modulates PTH1R downstream signaling in an agonist-dependent manner, most notably increasing the PTH-mediated Gi3 signaling sensitivity. Additionally, RAMP2 increases both PTH- and PTHrP-triggered β-arrestin2 recruitment to PTH1R. Employing homology modeling, we describe the putative structural molecular basis underlying our functional findings. These data uncover a critical role of RAMPs in the activation and signaling of a GPCR that may provide a new venue for highly specific modulation of GPCR function and advanced drug design.
|
|
| 5. |
|
|
